Sign in

A New Look at Cellulite, Part II

Peter T. Pugliese, MD August 2008 issue of Skin Inc. magazine
Woman doing yoga with apple in foreground

Part one of this two-part series, which ran in the July 2008 issue, discussed the causes of cellulite. Part two will take a look at the pathological changes in cellulite tissues, as well as a new treatment for cellulite.

Pathological changes in cellulite tissues

The first step in the genesis of cellulite is the initial breakdown of the collagen fibers that form the separation between the fatty compartments, called trabeculae. This process occurs during many years and is continuous. It starts at the same time that menses starts—menarche. Each month, a further MMP insult is sent out from the uterus to all parts of the body, wreaking havoc in the connective tissue. Just how estrogen ties in to this process, science does not know for certain, except that there is an inseparable relation between estrogen and MMPs. One thing that is known is that when the MMP destruction surges each month, there is no repair crew coming to set the tissue right again and clean up the mess wrought by the MMPs.

The second step is the release of fatty tissue, which was confined to the tight, though flexible, compartments. This fat now escapes and moves both upward and laterally through a maze of broken and tangled fibrous bands. Some bands are still tied to the muscle layer and connect to the bottom of the dermis, restraining the movement in certain areas of the thighs and buttocks. This is the cause of the undulating surface of the skin appearance of cellulite. It does not have an orange-peel appearance as has been described in the literature unless tightly compressed by hand.h At times the fat has been known to become painful, which has led some investigators to think this a panniculitis, or even a lipodystrophy of some type.i There may be some inflammatory component present when considering the degree of tissue destruction in the cellulite-involved area. All this tissue damage, all the MMPs and all the cytokines must leave a host of peptides and small cellular entities that are potentially antigenic.

The third and final destructive step is the continued cycling of the MMPs, and the return of the destruction of connective tissue. The body has only one month to get ready for another onslaught and another wave of havoc. This process will continue until menopause, but another culprit prepares to take the place of the menstrual cycle. During the child-bearing years, women gradually lose their production of collagen from the fibroblasts, and the secretion of MMPs increases to continue to break down the collagen, not only in the cellulite areas, but also just about everywhere there is connective tissue. At this time, the ovaries start to shut down and make less estrogen, but the adipose tissue takes up the slack. Women who are overweight—50 pounds or more, perhaps less—will continue to make estrogen via the adipocytes. The more adipocytes, the more estrogen is produced. So the estrogen and MMPs go on their merry way, leaving shattered lives in their wake, and there is little that can stop them—but they can be stopped.

A new treatment for cellulite

Following are specific treatment instructions for cellulite, and although it may not be the final word on cellulite, it is the best information that is currently available.

General measures. One of the first things a young medical student learns in medical school is the Latin saying, “ Noli nocere,” meaning “Do ye no harm.” I use this saying as the foundation of my new treatment recommendations for cellulite. Remember, you are treating seriously damaged tissue; tissue that has been sadly abused. So no rolling or suction or pressure or harsh chemicals or dissolving injections or liposuction. Also no baking, boiling or frying.

First, it is important to support this damaged tissue with a pair of support-type pantyhose, such as Alive or Supp-Hose, since Sheer Energy is not quite firm enough, but will do if preferred. The reason behind the use of support pantyhose is to provide additional support for the weakened tissues, and I care not a fig if it is not fashionable: take your choice, good-looking legs and support hose, or thongs and cellulite.

Support hose come with a plus. You will reduce your chances for getting spider veins and varicose veins, as well. You will shunt more blood up to your skin and head, with the result that your skin will look better and you will think better. About 40% of your circulating blood is in your legs and buttocks when you stand or sit. With support hose, you push this blood upstairs where it can do more good. When you walk, you will pump even more blood up the body. Furthermore, you will be less tired at the end of the day.

The next thing is food intake control; not a cure, but an ancillary treatment. Mainly, cut out sugars—all candies, cookies, pastries, ice cream and sodas of any kind, especially the diet type. Lay on the proteins of any form, some fat and complex carbohydrates, and a good slug of fruits and vegetables. Plan some walking every day; make a schedule that you can keep, and be realistic and honest.

Topicals. Make sure you apply these products about one hour before you go to bed. In the morning, if you can, apply them, then put on your pantyhose and go for a short walk of 10–20 minutes, longer if you can.

Many of these ingredients are new, but by the time this article reaches you, there will be some products on the market that contain them. The estrogen blocking agent, genistein, is a soy derivative. Look for this on the label of ingredients—if it is not there, don’t use the product. This a phytoestrogen, which is 1,000 times less potent than estradiol, one of your body’s natural estrogens. It works by getting into the estrogen receptors on the fibroblasts and blocking the natural estrogen from getting to them. Placed on your thighs and buttocks, it will not interfere with your periods.

Oligomeric proanthocyanidins are a group of highly effective antioxidants, as well as MMP inhibitors. They appear to combine with collagen, and thereby prevent the MMPs from attaching to their binding sites. This action makes them a key ingredient in the battle against cellulite. There are many sources, both topical and oral. Take 100–200 mg per day orally, depending on your weight. In a topical form, it should be no less than 0.5% and even as high as 1.5%. Sources are pine bark, grape seeds and sea buckthorn oil. Be sure that you are using a reliable source. Preventing the destructive action of MMP-1 is a critical step in treating cellulite.

Rebuilding collagen is the next step. Collagen is made in the dermis by fibroblasts, which are under the control of many hormones and other second messengers, as well as by physical forces from both inside and outside the skin. A major stimulator of collagen is asiatic acid, a complex triterpene that stimulates the fibroblasts to produce collagen.j It is also an anti-inflammatory and wound-healing agent. Asiatic acid is an expensive agent, and you may see it substituted with ursolic acid, which is also effective, but not as potent. It is always best to use asiatic acid with vitamin C (ascorbic acid) since the two ingredients maximize collagen production.

At this stage, the damage has been stopped and the tissue needs to be repaired. A good portion of the area’s fat needs to be cleaned up and returned back to good shape. With the proper compression and the addition of the above therapeutic agents, the fat will go back to its original configuration. To start this process, some of the displaced fat needs to be utilized. Keep in mind that fat is stored energy, so you need to pull that energy out of storage to reduce it. Fat contains nine kilocalories per gram, so it has quite a bit of energy, but, fortunately, you can use this fat without strenuous exercise. The key is to direct the body to use the fat on your thighs and buttocks by applying specific ingredients. You may recall from the first article about cellulite that fat is metabolized in a certain way. Figure 5 outlines that pathway, but we are adding a new activator—resveratrol—an ingredient found in red wine and many other natural substances that helps to prevent new fat cells from forming and helps to mobilize exiting fat cells.1

The following additional ingredients also should be present.

  • Coleus forskolii extract, which stimulates lipolysis
  • Theophylline, or theophylline acetate, which prevents enzyme phosphodiesterase from destroying cyclic adenosine monophosphate (AMP), a key stimulant of the beta receptor on the fat cell.
  • Carnitine, or acetyl carnitine, is needed to burn up more fatty acid because it is produced in the adipocytes. The carnitine will shuttle the fatty acids into the mitochondria where they are converted to carbon dioxide, water and energy. You need to understand this process well because it is essential to re-establish this fat in a normal manner. The only reason the body will pull this fat from the thighs and buttocks is because the area is being specifically targeted and stimulated with the correct ingredients. Once fatty acids are in the bloodstream at night, the body doesn’t really care where they are coming from.

Physical measures

There is no rational reason to use physical modalities, except perhaps well-executed lymphatic drainage. This process will provide a reduction in interstitial fluid and decrease some internal pressure, thus allowing for a better environment in which tissue repair can occur. Many estheticians are skilled in lymphatic drainage, but many are not, so make sure you have the proper skills to perform this modality. Heat sometimes helps, but only in the form of gentle heat; a skin temperature should not exceed 36°C. Walking with support hose is the best physical measure you can use.

I have explored the used of progesterone topically in the treatment of cellulite and find that the physiological effects of progesterone are multiple and diverse. Much of the research about this is very often contradictory and questionable.

The way forward

I have used this treatment in various formulations for more than two years, and the results have been very satisfactory, though they are still evolving. As more is learned of the complex nature of cellulite, its treatment will be able to be modified to more of a magic bullet approach. Before you undertake to use a method to treat cellulite, whatever it may be, make sure you fully understand the reason behind the method and what scientific data exists to support it.


Cellulite is a hormonally initiated disease driven by MMPs’ destruction of adipose connective tissue, which are derived from the menstrual cycle production. Because menses is cyclic in nature, there is no way to stop the effects of this process other than to block the action of the MMPs on the connective tissue. Cellulite is characterized by collagen dissolution and displacement of adipose tissue. Correction lies in inhibiting MMPs, reducing displaced fat and rebuilding collagen connective tissue. The role of external pressure as treatment modality is important. Therapeutic measures should not be harmful or heroic. Other than moderate hand massage associated with lymphatic drainage, no physical modalities provide a rational basis for their use in the treatment of cellulite. The concept of MMPs as etiological agents for cellulite provides a rational basis for effective treatment. (Learn more about the questions that still exist about this disease.)


1. Lagouge et al, Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell, 127 1–14 (2006)

Related Content



Figure 5

Metabolism of triglycerides

Next image >